Wojciech Kozubski

Poznan University of Medical Sciences, Posen, Greater Poland Voivodeship, Poland

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Publications (137)289.52 Total impact

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    ABSTRACT: To assess the prevalence of considerable burden among caregivers of stroke survivors at 6 months (Time 1) and 5 years after stroke (Time 2), to analyse changes in burden severity over time and to identify factors associated with the burden. Eighty eight patient/caregiver pairs were assessed. Caregiver burden was measured with the Caregiver Burden Scale. Socio-demographic, stroke-related and psychological characteristics were analysed as potential determinants of the burden. Exact multiple logistic regression was used to identify the predictive factors. Considerable burden was reported by 44% of the caregivers at Time 1 and 30% at Time 2. The burden was independently associated with caregivers' sense of coherence and amount of time spent caregiving at Time 1, and with caregivers' anxiety at Time 2. A significant proportion of the caregivers experienced considerable burden in the post-acute and chronic phases of stroke, although this proportion declined over time. Several characteristics were associated with the increased burden at different time points. All the independent predictors related to aspects of the carers. Programmes including education about coping strategies and time management, as well as respite care provision, could be beneficial and might help to reduce the burden of caregiving. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    Patient Education and Counseling 04/2015; DOI:10.1016/j.pec.2015.04.008 · 2.60 Impact Factor
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    ABSTRACT: The aim of this case-control study was to evaluate carotid hemodynamic variables and traditional cardiovascular risk factors in women with Hashimoto thyroiditis (HT). The study group consisted of 31 females with HT on levothyroxine (L-T4) and 26 euthyroid women with HT without L-T4 matched for age and body mass index (BMI) as controls. Carotid intima-media thickness (CIMT), carotid extra-media thickness (CEMT), and pulsatility indexes in common carotid artery (PI CCA) and in internal carotid artery (PI ICA) were measured. BMI, waist circumference, lipid profile, fasting glucose and insulin levels, and parameters of thyroid function [TSH, free thyroxine (FT4) and antithyroperoxidase antibodies (TPOAbs)] were assessed. The study and the control groups did not differ in age, BMI, waist circumference, lipid profile, fasting glucose, and insulin levels. Results are expressed as median (IQR). Treated HT group had higher FT4 levels than nontreated [17.13 (5.11) pmol/l vs. 14.7 (2.27) pmol/l; p=0.0011] and similar TSH [1.64 (2.08) IU/ml vs. 2.07 (3.14) IU/ml; p=0.5915]. PI CCA and PI ICA were higher in the study group than in controls (p=0.0224 and p=0.0477, respectively). The difference remained statistically significant for PI ICA and PI CCA after adjustment for other variables (coefficient=0.09487; standard error=0.04438; p=0.037 and coefficient=0.1786; standard error=0.0870; p=0.0449, respectively). CIMT and CEMT were similar in both groups (p=0.8746 and p=0.0712, respectively). Women with HT on L-T4 replacement therapy have increased PI in common and internal carotid arteries than nontreated euthyroid HT patients. Therefore, it seems that hypothyroidism, but not autoimmune thyroiditis per se, influences arterial stiffness. © Georg Thieme Verlag KG Stuttgart · New York.
    Hormone and Metabolic Research 02/2015; DOI:10.1055/s-0034-1398491 · 2.04 Impact Factor
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  • Justyna Rosińska, Maria Łukasik, Wojciech Kozubski
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    ABSTRACT: The diver's nervous system is extremely sensitive to high ambient pressure, which is the sum of atmospheric and hydrostatic pressure. Neurological complications associated with diving are a difficult diagnostic and therapeutic challenge. They occur in both commercial and recreational diving and are connected with increasing interest in the sport of diving. Hence it is very important to know the possible complications associated with this kind of sport. Complications of the nervous system may result from decompression sickness, pulmonary barotrauma associated with cerebral arterial air embolism (AGE), otic and sinus barotrauma, high pressure neurological syndrome (HPNS) and undesirable effect of gases used for breathing. The purpose of this review is to discuss the range of neurological symptoms that can occur during diving accidents and also the role of patent foramen ovale (PFO) and internal carotid artery (ICA) dissection in pathogenesis of stroke in divers. Copyright © 2014 Polish Neurological Society. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.
    Neurologia i neurochirurgia polska 01/2015; 49(1):45-51. DOI:10.1016/j.pjnns.2014.11.004 · 0.54 Impact Factor
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    ABSTRACT: Introduction Despite the growing body of literature on the consequences of providing non-professional care to stroke survivors, the determinants of caregiving burden are still not fully recognized. Identification of significant determinants can facilitate caregiver intervention programs. The aim of this study was to evaluate the level of burden borne by caregivers of stroke patients and to identify the most important determinants of burden at 6 months after hospitalization. Material and methods Data were collected from 150 pairs of stroke patients/caregivers. Caregiver burden was assessed on the Caregiver Burden scale (CB). Several characteristics were measured as potential predictors of the burden. Special attention was paid to the caregiver's sense of coherence (SOC) and anxiety. Regression analysis was employed to test the hypothesized relationships between these variables and the burden. Results Forty-seven percentage of the caregivers reported a substantial burden (severe or moderate). Caregiver SOC (p < 0.001), anxiety (p < 0.001) and the patients’ functional status (p < 0.001) were the most important predictors of the overall burden and the most consistent predictors of the majority of aspects included in the CB scale. Caregiver health, patient's gender, time spent caregiving and social support were also factors related to the burden. The identified predictors explained 67% of the variance in the overall burden. Conclusions Clinicians and other professionals should focus on the coping abilities of caregivers, their emotional state and the level of patients’ dependency, as these are the vital and modifiable factors affecting caregiver burden following stroke.
    Archives of Medical Science 10/2014; 10(5):941-50. DOI:10.5114/aoms.2014.46214 · 1.89 Impact Factor
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    ABSTRACT: Polimorfizm promotora genu G-308A TNFα a ryzyko udaru niedokrwiennego. Czynnik martwicy nowotworu alfa (TNFα) jest ważnym mediatorem immunologicznym i może współdziałać w zapoczątkowaniu i postępie udaru niedokrwiennego. Genetyka cząsteczki TNFα może mieć ważną rolę w ryzyku udaru. Najbardziej interesujący aspekt polimorfizmu G-308 A pozostaje niewyjaśniony, z powodu wielu różnic w wynikach badań. Różnice etniczne w badanych kohortach mogą stanowić jedną z przyczyn wystąpienia udaru niedokrwiennego. Nasz badany materiał dotyczył 101 chorych z udarem niedokrwiennym, w tym 30% zdiagnozowano jako udar lakunarny. Rozpoznanie było oparte na nagłym występowaniu objawów neurologicznych, trwających dłużej niż 24 godziny i potwierdzonych przez metody neuroobrazowania. Wszyscy badani byli Polakami rasy kaukaskiej. 100 przypadkowo wybranych osób bez objawów choroby naczyniowej ośrodkowego układu nerwowego stanowiło materiał kontrolny. Częstość występowania polimorfizmu G-308A genu TNFα była określana jak opisano przez Rubattu i wsp. /2005/ [11]. Rozdział genotypów w naszym materiale był podobny i nieistotny statystycznie pomiędzy chorymi i grupą kontrolną. Heterozygoty G/A były stwierdzone u 9% chorych i w 15% przypadków grupy kontrolnej, homozygoty A/A były stwierdzone u 5% chorych i tylko u 1 osoby kontrolnej, a G/G u 87% chorych i u 84% osobników kontrolnych. Nasze wyniki są więc negatywne odnośnie możliwego znaczenia polimorfizmu G-308A TNFα w ryzyku udaru niedokrwiennego u osób rasy kaukaskiej, żyjących w Polsce.
    Neurologia i neurochirurgia polska 10/2014; DOI:10.1016/j.pjnns.2014.09.007 · 0.54 Impact Factor
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    Alzheimer's and Dementia 07/2014; 10(4):P674. DOI:10.1016/j.jalz.2014.05.1213 · 17.47 Impact Factor
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    ABSTRACT: Despite a significant progress in prevention, treatment and management in the past decades, stroke remains the most common disabling chronic condition in adult population. It may be a source of serious temporary or permanent consequences. These consequences should be recognised and measured for defining and implementation of remedial interventions and for optimum utilisation of health care resources. The aim of this work was to present sequels of stroke, taking into account objective and subjective indices, as documented in the recent literature of the subject. Selected data on mortality and survival following stroke were presented, the up-to-date literature was reviewed and register-based prospective studies were presented on quality of life (QoL) in post-stroke patients. Systematic reviews and meta-analyses of randomised controlled trials (RCTs) were summed up, related to efficacy of interventions aimed at improving QoL of the patients. Moreover, the studies were reviewed on burden and QoL experienced by caregivers of post-stroke patients and results were summed up of RCT synthesis aimed at reducing the burden and at improving QoL in the caregivers. The analysed studies indicated that stroke exerts a long-term, negative effect on patients’ QoL, promoting a decrease in this measure and burdening a significant proportion of the family caregivers. The applied till now different interventions and programmes targeted at the patients and at their carers analysed in RCTs showed no or modest effects on improving of QoL or reducing the caregiver's burden.
    Neurologia i neurochirurgia polska 07/2014; 48(4). DOI:10.1016/j.pjnns.2014.07.004 · 0.54 Impact Factor
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    ABSTRACT: Alzheimer’s disease (AD), a progressive neurodegenerative disorder leads to production of β‐amyloid (Aβ) which accumulation, facilitated in apolipoprotein E (APOE) ε‐4 carriers, results in brain degeneration by apoptosis, which may arise from oxidative damage generated by Aβ and checkpoint proteins deregulation, such as p53. The aim of the study was to analyze the mutation status in highly conservative exon 7 of TP53 and APOE allele, as well as p53 protein level in AD patients and control subjects. The study on TP53 and APOE was performed on 29 AD patients and 16 control subjects. The TP53 exon 7 was analyzed in DNA extracted from blood by sequencing and APOE allele was determined by RT‐PCR mismatchprimer technique. The p53 protein level was determined in peripheral lymphocytes by Western Blotting. The sequencing of exon 7 of TP53 revealed the presence of two various mutations only in AD patients: a missense mutation C748A (P250T, 3.4%) present in an APOE ε‐3/ε‐4 allele carrier and a silent mutation C708T (Y236Y), found in 6 (20.1%) AD patients with various APOE genotypes (ε‐2/ε‐3, ε‐3/ε‐3 and ε‐3/ε‐4). The analysis of APOE showed ε‐3/ε‐3 genotype to be more common in control group (62.5%) than in AD patients (37.9%). The ε‐3/ε‐4 variant was more abundant in AD group (44.8%) as compared to controls (31.3%). Variant ε‐4/ε‐4 occurred in a single AD patient, whereas ε‐2/ε‐2 genotype was found only in a control subject. Our results indicated that in the AD group the p53 level was highest in APOE ε‐4 carriers and did not change significantly in control group. It is most likely that both: mutations in the TP53 gene and APOE status participate in the pathogenesis of AD.
    ApoE, ApoE Receptors & Neurodegeneration Symposium; 06/2014
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    ABSTRACT: Neurodegeneration with brain iron accumulation (NBIA) defines a heterogeneous group of progressive neurodegenerative disorders characterized by excessive iron accumulation in the brain, particularly affecting the basal ganglia. In the recent years considerable development in the field of neurodegenerative disorders has been observed. Novel genetic methods such as autozygosity mapping have recently identified several genetic causes of NBIA. Our knowledge about clinical spectrum has broadened and we are now more aware of an overlap between the different NBIA disorders as well as with other diseases. Neuropathologic point of view has also been changed. It has been postulated that pantothenate kinase-associated neurodegeneration (PKAN) is not synucleinopathy. However, exact pathologic mechanism of NBIA remains unknown. The situation implicates a development of new therapies, which still are symptomatic and often unsatisfactory. In the present review, some of the main clinical presentations, investigational findings and therapeutic results of the different NBIA disorders will be presented.
    Neurologia i neurochirurgia polska 05/2014; 48(3):206-213. DOI:10.1016/j.pjnns.2014.05.001 · 0.54 Impact Factor
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    ABSTRACT: Abstract BACKGROUND: Subcutaneous pegylated interferon (peginterferon) beta-1a is being developed for treatment of relapsing multiple sclerosis, with less frequent dosing than currently available first-line injectable treatments. We assessed the safety and efficacy of peginterferon beta-1a after 48 weeks of treatment in the placebo-controlled phase of the ADVANCE trial, a study of patients with relapsing-remitting multiple sclerosis. METHODS: We did this 2-year, double-blind, parallel group, phase 3 study, with a placebo-controlled design for the first 48 weeks, at 183 sites in 26 countries. Patients with relapsing-remitting multiple sclerosis (age 18-65 years, with Expanded Disability Status Scale score ≤5) were randomly assigned (1:1:1) via an interactive voice response or web system, and stratified by site, to placebo or subcutaneous peginterferon beta-1a 125 μg once every 2 weeks or every 4 weeks. The primary endpoint was annualised relapse rate at 48 weeks. This trial is registered with ClinicalTrials.gov, number NCT00906399. FINDINGS: We screened 1936 patients and enrolled 1516, of whom 1512 were randomly assigned (500 to placebo, 512 to peginterferon every 2 weeks, 500 to peginterferon every 4 weeks); 1332 (88%) patients completed 48 weeks of treatment. Adjusted annualised relapse rates were 0·397 (95% CI 0·328-0·481) in the placebo group versus 0·256 (0·206-0·318) in the every 2 weeks group and 0·288 (0·234-0·355) in the every 4 weeks group (rate ratio for every 2 weeks group 0·644, 95% CI 0·500-0·831, p=0·0007; rate ratio for the every 4 weeks group 0·725, 95% CI 0·565-0·930, p=0·0114). 417 (83%) patients taking placebo, 481 (94%) patients taking peginterferon every 2 weeks, and 472 (94%) patients taking peginterferon every 4 weeks reported adverse events including relapses. The most common adverse events associated with peginterferon beta-1a were injection site reactions, influenza-like symptoms, pyrexia, and headache. 76 (15%) patients taking placebo, 55 (11%) patients taking study drug every 2 weeks, and 71 (14%) patients taking study drug every 4 weeks reported serious adverse events; relapse, pneumonia, and urinary tract infection were the most common. INTERPRETATION: After 48 weeks, peginterferon beta-1a significantly reduced relapse rate compared with placebo. The drug might be an effective treatment for relapsing-remitting multiple sclerosis with less frequent administration than available treatments.
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    ABSTRACT: Abstract BACKGROUND: Subcutaneous pegylated interferon (peginterferon) beta-1a is being developed for treatment of relapsing multiple sclerosis, with less frequent dosing than currently available first-line injectable treatments. We assessed the safety and efficacy of peginterferon beta-1a after 48 weeks of treatment in the placebo-controlled phase of the ADVANCE trial, a study of patients with relapsing-remitting multiple sclerosis. METHODS: We did this 2-year, double-blind, parallel group, phase 3 study, with a placebo-controlled design for the first 48 weeks, at 183 sites in 26 countries. Patients with relapsing-remitting multiple sclerosis (age 18-65 years, with Expanded Disability Status Scale score ≤5) were randomly assigned (1:1:1) via an interactive voice response or web system, and stratified by site, to placebo or subcutaneous peginterferon beta-1a 125 μg once every 2 weeks or every 4 weeks. The primary endpoint was annualised relapse rate at 48 weeks. This trial is registered with ClinicalTrials.gov, number NCT00906399. FINDINGS: We screened 1936 patients and enrolled 1516, of whom 1512 were randomly assigned (500 to placebo, 512 to peginterferon every 2 weeks, 500 to peginterferon every 4 weeks); 1332 (88%) patients completed 48 weeks of treatment. Adjusted annualised relapse rates were 0·397 (95% CI 0·328-0·481) in the placebo group versus 0·256 (0·206-0·318) in the every 2 weeks group and 0·288 (0·234-0·355) in the every 4 weeks group (rate ratio for every 2 weeks group 0·644, 95% CI 0·500-0·831, p=0·0007; rate ratio for the every 4 weeks group 0·725, 95% CI 0·565-0·930, p=0·0114). 417 (83%) patients taking placebo, 481 (94%) patients taking peginterferon every 2 weeks, and 472 (94%) patients taking peginterferon every 4 weeks reported adverse events including relapses. The most common adverse events associated with peginterferon beta-1a were injection site reactions, influenza-like symptoms, pyrexia, and headache. 76 (15%) patients taking placebo, 55 (11%) patients taking study drug every 2 weeks, and 71 (14%) patients taking study drug every 4 weeks reported serious adverse events; relapse, pneumonia, and urinary tract infection were the most common. INTERPRETATION: After 48 weeks, peginterferon beta-1a significantly reduced relapse rate compared with placebo. The drug might be an effective treatment for relapsing-remitting multiple sclerosis with less frequent administration than available treatments.
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    ABSTRACT: Hyperhomocysteinemia is a well-known cardiovascular risk factor and its elevation is established in overt hypothyroidism. Since some authors suggest that chronic autoimmune thyroiditis per se may be considered as a novel risk factor of atherosclerosis independent of thyroid function, the analysis of classical cardiovascular risk factors might be helpful in evaluation the causative relationship. Data concerning the impact of thyroid autoimmunity in euthyroid state on homocysteine (Hcy) level is lacking. The aim of this study was to evaluate Hcy level in context of anti-thyroperoxidase antibodies (TPOAbs) in euthyroidism. It is a case-control study. 31 euthyroid women treated with levothyroxine (L-T4) due to Hashimoto thyroiditis (HT) and 26 females in euthyroidism without L-T4 replacement therapy were enrolled in the study. All women with HT had positive TPOAbs. Forty healthy females negative for TPOAbs comparable for age and body mass index (BMI) participated in the study as controls. Exclusion criteria were a history of any acute or chronic disease, use of any medications (including oral contraceptives and vitamin supplements), smoking, alcoholism. TPOAbs titers were higher in both groups of HT patients versus the healthy controls. Hcy levels were found to be significantly lower in treated HT patients (Me 11 mumol; IQR 4.2 mumol) as compared with healthy controls (Me 13.35 mumol; IQR 6.34 mumol; p = 0.0179). In contrast, no significant difference was found between non treated HT and control group in Hcy level. The study groups and the controls did not differ in age and BMI. Furthermore, levels of TSH, FT4, TC, LDL, HDL and TAG did not differ between the study group and the control group. The main finding of the study is a decrease in Hcy level in treated HT as compared with healthy controls. Based on our observations one can also assume that correct L-T4 replacement was associated here with a decrease of Hcy. Furthermore, it seems that non treated HT in euthyroidism is not associated with Hcy increase, in contrast to overt hypothyroidism. This may be just another argument against the concepts about the role of "euthyroid HT" in the development of atherosclerosis.
    BMC Endocrine Disorders 03/2014; 14(1):18. DOI:10.1186/1472-6823-14-18 · 1.67 Impact Factor
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    Piotr Iwanowski, Wojciech Kozubski, Jacek Losy
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    ABSTRACT: Nummular headache (NH) is a rarely recognized primary headache, the diagnostic criteria of which are contained in the appendix to the 2nd edition of the International Classification of Headache Disorders (code A13.7.1). We present the case of a 61-year-old female who suffers, regardless of NH, from right-sided occipital neuralgia. The applied treatment - gabapentin and mianserin - had no effect. Injection of bupivacaine twice to the right occipital region resulted in neuralgia resolution up to three months, with no effect on NH. This confirms the independence of two abovementioned head pain conditions.
    Neurologia i neurochirurgia polska 03/2014; 48(2):141-3. DOI:10.1016/j.pjnns.2013.09.005 · 0.54 Impact Factor
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    ABSTRACT: Knowledge on the genetics of movement disorders has advanced significantly in recent years. It is now recognized that disorders of the basal ganglia have genetic basis and it is suggested that molecular genetic data will provide clues to the pathophysiology of normal and abnormal motor control. Progress in molecular genetic studies, leading to the detection of genetic mutations and loci, has contributed to the understanding of mechanisms of neurodegeneration and has helped clarify the pathogenesis of some neurodegenerative diseases. Molecular studies have also found application in the diagnosis of neurodegenerative diseases, increasing the range of genetic counseling and enabling a more accurate diagno-sis. It seems that understanding pathogenic processes and the significant role of genetics has led to many experiments that may in the future will result in more effective treatment of such diseases as Parkinson's or Huntington's. Currently used molecular diagnostics based on DNA analysis can identify 9 neurodegenerative diseases, including spinal cerebellar ataxia inherited in an autosomal dominant manner, dentate-rubro-pallido-luysian atrophy, Friedreich's disease, ataxia with ocu-lomotorapraxia, Huntington's disease, dystonia type 1, Wilson's disease, and some cases of Parkinson's disease.
    Current Genomics 02/2014; 15(1):18-27. DOI:10.2174/1389202914666131210213327 · 2.87 Impact Factor
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    ABSTRACT: Parkinson's disease (PD) is one of the most common neurological diseases in elderly people. The mean age of onset is 55 years of age, and the risk for developing PD increases 5-fold by the age of 70. In PD, there is impairment in both motor and nonmotor (NMS) functions. The strategy of PD motor dysfunction treatment is simple and generally based on the enhancement of dopaminergic transmission by means of the L-dihydroxyphenylalanine (L-dopa) and dopamine (DA) agonists. L-dopa was discovered in the early -60's of the last century by Hornykiewicz and used for the treatment of patients with PD. L-dopa treatment in PD is related to decreased levels of the neurotransmitter (DA) in striatum and ab-sence of DA transporters on the nerve terminals in the brain. L-dopa may also indirectly stimulate the receptors of the D1 and D2 families. Administration of L-dopa to PD patients, especially long-time therapy, may cause side effects in the form of increased toxicity and inflammatory response, as well as disturbances in biothiols metabolism. Therefore, in PD pa-tients treated with L-dopa, monitoring of oxidative stress markers (8-oxo-2'-deoxyguanosine, apoptotic proteins) and in-flammatory factors (high-sensitivity C-reactive protein, soluble intracellular adhesion molecule), as well as biothiol com-pounds (homocysteine, cysteine, glutathione) is recommended. Administration of vitamins B6, B12, and folates along with an effective therapy with antioxidants and/or anti-inflammatory drugs at an early stage of PD might contribute to improvement in the quality of the life of patients with PD and to slowing down or stopping the progression of the disease.
    Current Genomics 02/2014; 15(1):11-7. DOI:10.2174/1389202914666131210213042 · 2.87 Impact Factor
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    ABSTRACT: Alzheimer’s disease (AD) leads to generation of β-amyloid (Aβ) in the brain. Alzheimer’s disease model PS/APP mice show a markedly accelerated accumulation of Aβ, which may lead to apoptosis induction e.g. in cells expressing wild-type p53. The TP53 gene is found to be the most frequently mutated gene in human tumour cells. There is accumulating evidence pointing out to the contribution of oxidative stress and chronic inflammation in both AD and cancer. The purpose of this study was to analyze exon 7 mutations of the murine Trp53 gene and Aβ/A4 and p53 protein levels in PS/APP and control mice. The studies were performed on female double transgenic PS/APP mice and young adults (8-12 weeks old) and agematched control mice. The Trp53 mutation analysis was carried out with the use of PCR and DNA sequencing. The Aβ/A4 and p53 levels were analyzed by Western blotting. The frequency of mutations was almost quadrupled in PS/APP mice (44%), compared to controls (14%). PS/APP mice with the A929T and A857G mutations had a similar p53 level. In cerebral gray matter of PS/APP mice the level of p53 positive correlated with the level of Aβ protein (RS = +0.700, p < 0.05). In younger control animals, the T854G mutation was related to p53 down-regulation, while in aging ones, G859A substitution was most likely associated with over-expression of p53. In silico protein analysis revealed a possibly substantial impact of all four mutations on p53 activity. Three mutations were in close proximity to zinc-coordinating cysteine residues. It seems that in PS/APP mice missense Trp53 exon 7 mutations may be associated with the degenerative process by changes of p53 protein function.
    Folia Neuropathologica 01/2014; 52(1):30-40. DOI:10.5114/fn.2014.41742 · 1.67 Impact Factor
  • Anna Oczkowska, Wojciech Kozubski, Jolanta Dorszewska
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    ABSTRACT: Parkinson's disease (PD) is a degenerative disease of the central nervous system, of which patomechanizm entirely is not clear. In the picture neuropathologically there is observed degeneration and loss of dopaminergic neurons, but also noradrenergic, serotonergic and cholinergic neurons in patients with PD. It is believed, that causes of PD are both environmental and genetic factors, associated mainly with mutations in the SNCA and PRKN genes, which may lead to changes in the structure of proteins such as alpha-synuclein (ASN) and Parkin. In neurons, disorders of the protein structure can lead to its aggregation and formation of soluble oligomers and insoluble filaments in the form of Lewy bodies and Lewy neuritis. In PD aggregation of ASN can be modulated by many factors like: oxidative stress, other neuronal proteins, Parkin, catecholamines especially dopamine, and mutations of SNCA gene. It also appears that some impact on the aggregation of ASN may have destabilizing factors of ASN tetramers. That, does ASN may become a new point for pharmacotherapy in PD.
    Przegla̧d lekarski 01/2014; 71(1):26-32.
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    ABSTRACT: Alzheimer’s disease (AD) leads to the generation of β-amyloid (Aβ), which may damage DNA and thus lead to apoptosis induction by the p53 pathway. Dysfunction of the p53 protein may then be connected with the development of AD. Studies were conducted on 28 AD patients and 30 non-AD controls. Analysis of TP53 mutations in exon 7 was performed on DNA isolated from whole blood and biochemical parameters in the peripheral lymphocytes of these individuals. Our study showed a silent mutation TP53 C708T (21%) [p < 0.05] and a missense mutation TP53 C748A (4%) only in the AD patients. Moreover, in AD patients with the TP53 C748A mutation, the level of 8-oxo-2’- deoxyguanosine (8-oxo2dG) was more than 5 times higher than the average level in this study group. In AD patients with the wild-type TP53 gene, the level of 8-oxo2dG was correlated with the level of protein p53 (R = +0.7388, p < 0.05). The level of the oxoguanine DNA glycosylase 1 (OGG1) protein was similar in AD patients with the silent mutation and the wild-type gene TP53 (p < 0.05) and lower than in the controls. It appears that mutations in exon 7 of TP53 (C748A, C708T) may be associated with pathogenesis of AD.
    Advances in Alzheimer's Disease 01/2014; 3(1):24-32. DOI:10.4236/aad.2014.31004

Publication Stats

467 Citations
289.52 Total Impact Points

Institutions

  • 1999–2015
    • Poznan University of Medical Sciences
      • • Department of Metabolism Endocrinology and Internal Medicine
      • • Department of Neurology
      Posen, Greater Poland Voivodeship, Poland
  • 2009–2012
    • Uniwersytet Medyczny im.Karola Marcinkowskiego w Poznaniu
      Posen, Greater Poland Voivodeship, Poland
  • 2004
    • Polish Academy of Sciences
      • Institute of Human Genetics
      Warsaw, Masovian Voivodeship, Poland
  • 2003
    • Poznańskie Centrum Superkomputerowo-Sieciowe
      Posen, Greater Poland Voivodeship, Poland